Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics | RCV000517203 | SCV000615709 | uncertain significance | not specified | 2017-04-28 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000794270 | SCV000933665 | uncertain significance | Emery-Dreifuss muscular dystrophy 5, autosomal dominant | 2024-05-29 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 3850 of the SYNE2 protein (p.Asp3850Gly). This variant is present in population databases (no rsID available, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with SYNE2-related conditions. ClinVar contains an entry for this variant (Variation ID: 448624). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glycine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Revvity Omics, |
RCV000794270 | SCV003820823 | uncertain significance | Emery-Dreifuss muscular dystrophy 5, autosomal dominant | 2019-09-09 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000517203 | SCV005203659 | likely benign | not specified | 2024-07-05 | criteria provided, single submitter | clinical testing | Variant summary: SYNE2 c.11549_11550delinsGA (p.Asp3850Gly) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele is composed of two neighboring single nucleotide variants, which are found with almost identical allele numbers, and are reported in at least 376 / 1614038 alleles, i.e. at a frequency of 0.00023 in the gnomAD database v4.1 dataset, and database also noted that these variants are found in phase in (at least) 14 of the reported 18 carriers in the v2.1 dataset. The occurrence of the variant in several carriers suggests that this variant is likely not associated with high penetrance, severe, early onset disease phenotype in heterozygous state. The two component variants have been reported in the literature in an individual with suspected limb-girdle muscular dystrophy (Kuhn_2016), however the patient had negative family history. This report does not provide unequivocal conclusions about association of the variant with Emery-Dreifuss Muscular Dystrophy 5, Autosomal Dominant. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. ClinVar contains an entry for this variant (Variation ID: 448624). Based on the evidence outlined above, the variant was classified as likely benign. |